The purpose of the study is to examine the safety of a 14 day infusion of sodium nitrite, and to study the pharmacokinetics of nitrite, during a 14 day infusion in patients with ruptured cerebral aneurysms.

Mean Plasma Nitrite Concentration (Micromol/L) [ Time Frame: multiple time points up to the end of day 14 ] [ Designated as safety issue: Yes ]

Samples for pharmacokinetic analysis were collected from subjects treated with sodium nitrite at -15, -5, 0, 10, 30, 60, and 90 minutes after starting nitrite infusion and then at 2, 4, 6, 8, 12, 24, and every 24 hours after starting nitrite infusion. The sample at the time of starting the infusion was considered to be the time 0 sample. On study day 14 additional blood samples were collected at 0, 10, 30, 60, and 90 minutes and at 2, 4, 6, 8, and 12 hours after stopping nitrite infusion. Blood samples were analyzed for nitrite levels using mass spectroscopy.

Secondary Outcome Measures:

Safety of a 14 Day Infusion of Sodium Nitrite [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]

Efficacy of 14 Day Infusion of Sodium Nitrite [ Time Frame: 14 days ] [ Designated as safety issue: No ]

14 day continuous infusion of one of 3 escalating doses of sodium nitrite: 32 nmol/min/kg, 48 nmol/min/kg, or 64 nmol/min/kg

Other Name: Sodium Nitrite Injection NDC 60267-311-10

Placebo Comparator: Vehicle control

Continuous intravenous infusion of saline

Drug: Saline

14 day continuous infusion of a vehicle control infusion

Other Name: Sterile saline

Detailed Description:

Intravenous sodium nitrite has been shown to prevent and to reverse cerebral vasospasm in a primate model of subarachnoid hemorrhage (SAH). This was a Phase IIA dose escalation study of sodium nitrite to determine its safety in patients with aneurysmal SAH and to establish its pharmacokinetics during a 14 day infusion.

Sodium nitrite was delivered intravenously for 14 days in 18 patients with SAH from a ruptured cerebral aneurysm using a dose escalation scheme in three cohorts of 6 patients each (3 nitrite, 3 saline), with a maximum dose of 64 nmol/min/kg. Sodium nitrite blood levels were frequently sampled and measured using mass spectroscopy and blood methemoglobin levels were continuously monitored using a pulse oximeter.

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00873015